"These findings published today in the Journal for ImmunoTherapy of Cancer demonstrate IL-15's mechanism of action for engaging natural killer cell biology for the treatment of cancers," said Dr.
"The findings in JITC describe the foundational science behind NKTR-255 and support its clinical advancement in both liquid and solid tumors," said Jonathan Zalevsky, Ph.D., Chief Research & Development Officer at Nektar. "We look forward to results from our two Phase 1/2 studies designed to evaluate NKTR-255 as a monotherapy as well as in combination with leading antibody-dependent cellular toxicity compounds, rituximab and daratumumab in hematological malignancies, and cetuximab in solid tumors."
Researchers analyzed in vitro pharmacological properties of rhIL-15, NKTR-255 and precomplexed IL-15 cytokines (rhIL-15/IL-15Ra and rhIL-15 N72D/IL-15Rα Fc) in receptor binding, cell signaling and cell function assays. In vivo pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the cytokines were evaluated in normal mice, and immunomodulatory effect and anti-tumor activity were assessed in a model of lymphoma.
Key findings are summarized below:
- NKTR-255 maintained a similar receptor binding profile to that of rhIL-15, as compared to precomplexed IL-15 agonists.
- In vivo, NKTR-255 exhibited a PK profile with reduced clearance and a longer half-life (clearance: 2.31 mL/hour/kg; effective half-life: 15.2 hours) relative to rhIL-15 (clearance: 507 mL/hour/kg; effective half-life: 0.168 hours); NKTR-255 also demonstrated prolonged IL-15R engagement in lymphocytes compared with only transient engagement observed for rhIL-15 and precomplexed rhIL-15 N72D/IL-15Rα Fc.
- NKTR-255 was shown to provide a more durable and sustained effect on proliferation and activation of NK and CD8+ T cells than precomplexed cytokines.
- The properties of NKTR-255 promoted elevations in functionally competent cytotoxic NK cells in the tumor microenvironment and overall translated into increased survival rates and superior antitumor activity in a B-cell lymphoma model versus the precomplexed cytokines.
NKTR-255 is currently being evaluated in multiple clinical studies in both hematologic malignancies and solid tumors as a monotherapy and in combination with agents that induce antibody-dependent cellular toxicity (ADCC). In the hematological setting, NKTR-255 is being tested in a Phase 1b/2 clinical study as monotherapy and in combination with rituximab or daratumumab in patients with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). It is also being evaluated in a Phase 1b/2 solid tumor trial in combination with cetuximab for the treatment of colorectal cancer (CRC) and head and neck squamous cell carcinoma (HNSCC).
NKTR-255 is a novel polyethylene glycol (PEG)-conjugate of recombinant human Interleukin-15 (rhIL-15), which was designed to retain all known receptor binding interactions of the IL-15 molecule.
NKTR-255 is uniquely designed to overcome the challenges of recombinant IL-15 and other IL-15 agonists, which are rapidly cleared from the body and have shown diminishing response to successive doses. Through an extended circulating half-life and optimal engagement of the IL-15Rα/IL-2Rβγ receptor complex, NKTR-255 enhances functional NK cell populations and formation of long-term CD8+ mediated immunological memory, which may lead to sustained anti-tumor immune response.
The full citation of this article can be accessed at: Miyazaki T, Maiti M, Hennessy M, et al. NKTR-255, a novel polymer-conjugated rhIL-15 with potent antitumor efficacy.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements which can be identified by words such as: "may," "design," "potential," "provide," "support" and similar references to future periods. Examples of forward-looking statements include, among others, statements we make regarding the therapeutic potential of, and future development plans for NKTR-255 in both liquid and solid tumors. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause our actual results to differ materially from those indicated in the forward-looking statements include, among others: (i) our statements regarding the therapeutic potential of NKTR-255 are based on preclinical and clinical findings and observations and are subject to change as research and development continue; (ii) NKTR-255 is an investigational agent and continued research and development for this drug candidate is subject to substantial risks, including negative safety and efficacy findings in ongoing clinical studies (notwithstanding positive findings in earlier preclinical and clinical studies); (iii) NKTR-255 is in early clinical development and the risk of failure is high and can unexpectedly occur at any stage prior to regulatory approval; (iv) the timing of the commencement or end of clinical trials and the availability of clinical data may be delayed or unsuccessful due to regulatory delays, slower than anticipated patient enrollment, manufacturing challenges, changing standards of care, evolving regulatory requirements, clinical trial design, clinical outcomes or competitive factors; (v) patents may not issue from our patent applications for our drug candidates, patents that have issued may not be enforceable, or additional intellectual property licenses from third parties may be required; and (vi) certain other important risks and uncertainties set forth in our Quarterly Report on Form 10-Q filed with the
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